Contact allergy due to colophony (VI). The sensitizing capacity of minor resin acids and 7 commercial modified-colophony products.

3 minor resin acids and 7 commercial modified-colophony products of different origins were studied by experimental sensitization by means of a modified FCA method. All 3 resin acids were almost negative. The commercial products gave different results. While the maleic-modified product of Greek origin showed a strong sensitizing power, the fumaric-modified, terpene-phenol-modified and a disproportioned rosin were only moderate. A remarkable difference was obtained with the Swedish and Finnish tall oil rosins, which, in contrast to the previously studied French product, exhibited only a weak sensitizing capacity.

Brain electrical imaging the dose-response effects of cigarette smoking.

Quantitative regional electroencephalographic (EEG) effects of cigarette smoking were examined within a repeated measures design which assessed, and topographically displayed, changes in power spectral estimates resulting from the smoking of low, medium and high tar/nicotine (T/N) yield cigarettes. Although intercigarette yield comparisons revealed no significant EEG differences between yields, comparison of the effects of smoking each yield with sham smoking indicated the presence of a qualitative dose-response effect whereby increasing T/N yields resulted in a progressive posterior-to-anterior spreading of significant relative power changes within both theta and alpha frequency bands. These exploratory findings are discussed in relation to smoking maintenance and working hypotheses are formulated for future testing.

Dosimetric equivalence of tar deposition in rodents and man.

It has proved very difficult to produce cancer in laboratory animals following the inhalation of tar from cigarette smoke. Amongst other factors, this may be due to the dose that animals get in comparison to humans. Data reported here suggest that the average dose to the bronchial region of the lung, estimated using radiotracer techniques, may be a factor of 4 lower. The local dose to the carinal is also discussed; this may be lower still.

[Effects of combined administration of alcohol and tobacco on the ultrastructure of ventricular cardiomyocytes in rats]. / Wplyw skojarzonego dzialania alkoholu i tytoniu na ultrastrukture kardiomiocytów komory serca szczurów.

Ultrastructural changes of rat ventricular cardiomyocytes after ethanol and tobacco tar was investigated. Lesions was found in mitochondria, endoplasmic reticulum and amount of the glycogen. This changes was more pronounced in males then in females. Negative influence are correlated to time of experiment.

Smoking and lung cancer: risk as a function of cigarette tar content.

The hypothesis of reduction in lung cancer risk associated with the adoption of low-tar cigarettes was examined in a subset of subjects from a population-based, case-control study of incident primary lung cancer among New Jersey white men. Risk was related to time-weighted average tar levels of cigarettes smoked in 1973-1980. Unadjusted estimates of risk were significantly low for the lowest tar (less than 14 mg/cig) smokers [odds ratio = 0.53 (0.29,0.97)] compared with the highest (21.1-28 mg/cig). However, adjustment by age and total pack-years rendered the risk reduction insignificant. Of note was the finding that cases who smoked low-tar cigarettes compensated for reducing tar by increasing the number of cigarettes they smoked by almost half a pack per day from the years 1963-1972 to 1973-1980, while in the same period controls and high-tar cigarette smoking cases did not increase the numbers smoked.

Behavioral and biochemical effects of gradual reductions in cigarette yields in pregnant and nonpregnant smokers.

Smoking-related risks have been well-documented for both the smoker and the pregnant smoker's unborn child, but the risks associated with low tar/nicotine cigarette smoking are still controversial. The present study examined some of the behavioral and biochemical effects of gradual reductions in tar and nicotine yields in six pregnant and six nonpregnant smokers. Over four sessions spanning a 6-week period, smokers switched to cigarette brands progressively lower in tar and nicotine. Examination of the topographical variables assessed both during (cigarette frequency, puff frequency, and cigarette duration) and between sessions (daily cigarette rate and nicotine intake) revealed significant decreases in both pregnant and nonpregnant smokers' cigarette duration and nicotine intake. Also observed were significantly lower and less variable carboxyhemoglobin (COHb) levels among the pregnant smokers when they smoked the lowest tar and nicotine brands. However, even the pregnant smokers' lower mean COHb levels did not drop below the 3% minimal cardiovascular risk level. The pregnant smokers also tended to have lower and less variable salivary thiocyanate (SCN) levels, but these differences were nonsignificant. The results were discussed in terms of implications for controlled smoking treatment programs for pregnant smokers.

Tissue distribution of covalent DNA damage in mice treated dermally with cigarette 'tar': preference for lung and heart DNA.

The high incidence of lung cancer in smokers is thought to be related to the direct exposure of bronchial and pulmonary cells to carcinogens in inhaled cigarette smoke. Using a 32P-postlabeling assay for chemically induced covalent DNA alterations, we found that unfractionated, relatively non-polar cigarette smoke components bound preferentially to lung and heart DNA in female ICR mice. After 6 days of topical treatment with cigarette smoke condensate (CSC) equivalent to a total of 4.5 cigarettes, covalent DNA damages was estimated to be 6.2, 5.7, 3.9 and 1.9 times higher, respectively, in lung, heart, skin and kidney than in liver, ranging from approximately 1 adduct in 5.4 +/- 0.7 X 10(6) DNA nucleotides in lung to 1 adduct in 3.3 +/- 0.6 X 10(7) DNA nucleotides in liver. Spleen DNA was virtually adduct-free. Adducts occupied two extensive zones, designated diagonal radioactive zone (DRZ) 1 and DRZ 2, on TLC fingerprints. Preference for lung and heart DNA was also observed in mice treated for 1 or 3 days. An inverse association appeared to exist between the tissue distribution of CSC-induced covalent DNA damage and the reported activity of enzymes catalyzing the metabolism of xenobiotics (cytochrome P-450 monooxygenases, phase II enzymes) and toxic oxygen species (superoxide dismutase, catalase). The results suggest that the well-known pulmonary and cardiovascular organotropism of cigarette-smoking-associated adverse health effects may, in part, have its origin in the inherent capacity of cigarette smoke components to induce lesions in lung and heart DNA in a tissue-specific manner. Possible mechanisms and health implications of the preferential binding of presumably aromatic CSC constituents to lung and heart DNA are discussed.

Refined cigarette smoke as a method for reducing nicotine intake.

We developed a method of refining tobacco smoke to deliver sensory components of cigarette smoking while minimizing the delivery of nicotine and other toxic smoke constituents. In the first experiment, smokers rated puffs of their own brands of cigarette, a commercial low tar and nicotine cigarette, and refined smoke. The refined smoke was rated significantly stronger and more desirable than the low tar and nicotine cigarette despite a comparably low nicotine delivery; subjects' own brands were rated best, but in standardized smoking tests delivered over ten times more tar, nicotine and carbon monoxide. In the second experiment, subjects smoked five times on each of two mornings; one day they received refined smoke and the other day smoked a low tar and nicotine cigarette. The refined smoke produced significantly more satisfaction, yet delivered far less carbon monoxide and tar (assessed by mouth intake). Nicotine intake was comparable to that of the low tar and nicotine cigarette. Because refined smoke substantially reduced subjects' craving for cigarettes while reducing nicotine intake, it may prove to be a useful short-term adjunct to a smoking cessation program. Additionally, the method may be useful in research analyzing the relative contributions of pharmacologic actions of inhaled smoke and the sensory cues associated with nicotine intake as reinforcers maintaining smoking behavior.

[Skin reaction to dithranol and its modification by the addition of tar (LCD)]. / Hautreaktion auf Dithranol und ihre Beeinflussung durch Teerzusatz (LCD).

In spite of 70 years' continuous use of dithranol for the topical treatment of psoriasis, there are few reports of contact hypersensitivity reactions to this compound. A male patient with psoriasis had an adverse skin reaction to the traditional topical dithranol treatment; patch tests revealed contact dermatitis in response to 0.02% dithranol in petrolatum, which was characterized by marked erythema and severe bullous reaction to 0.1% dithranol in acetone. A control group of ten volunteers tested under similar conditions did not react with marked erythema until a concentration of 0.1% dithranol in petrolatum was applied. When liquid tar (5% liquor carbonis detergens, LCD) was added to the patch test solutions concentrations that were clearly one or two steps higher were needed before the erythematous skin reaction was induced. Since minimal erythema generally appears in patch tests with greater than or equal to 0.05% dithranol in petrolatum, we believe that in the patient reported here contact hypersensitivity to dithranol was present. The development of large perilesional erythematous areas with accompanying edema during topical dithranol treatment supports this suggestion. It seems that the addition of liquid tar elevates the reaction threshold to dithranol in hypersensitive patients with psoriasis.

The separate effects of tar and nicotine on the cigarette smoking manoeuvre.

The separate effects of tar and nicotine on the cigarette smoking manoeuvre were investigated. Each of ten asymptomatic habitual smokers smoked three different commercially available cigarettes in a randomised order. The brands were chosen such that two had the same tar yield (10 mg) and two had the same nicotine yield (1.4 mg). The volume of smoke inhaled into the lungs was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded using an electronic smoking analyser and flowhead/cigarette holder. There was no difference in the total volume of smoke puffed from each of the cigarette brands. With cigarettes of the same tar level, the total inhaled smoke volume was lower with the higher nicotine cigarette (P less than 0.05): by contrast, with cigarettes of the same nicotine level, the total inhaled smoke volume was lower with the lower tar cigarette (P less than 0.02). Tar and nicotine appear to exercise independent control over the volume of smoke inhaled.

Influence of smoking fewer cigarettes on exposure to tar, nicotine, and carbon monoxide.

In the hope of reducing the adverse health consequences of smoking, physicians frequently advise their patients who cannot quit to smoke fewer cigarettes. Habitual smokers may compensate for the reduced number of cigarettes, however, by taking in more smoke per cigarette. We measured the intake of tar (estimated as mutagenic activity of the urine), nicotine, and carbon monoxide during short-term cigarette restriction. With a reduction from an average of 37 cigarettes to an average of 5 cigarettes per day, the intake of tobacco toxins per cigarette increased roughly threefold and daily exposure to tar and carbon monoxide declined only 50 percent. We conclude that smoking fewer cigarettes may reduce exposure to toxins and related adverse health consequences. However, consistent with a tendency to maintain intake of nicotine, the magnitude of the benefit is much less than expected. Whether "oversmoking" persists during long-term restriction of cigarettes requires further investigation.

Reduced tar, nicotine, and carbon monoxide exposure while smoking ultralow- but not low-yield cigarettes.

An unresolved public health issue is whether some modern cigarettes are less hazardous than others and whether patients who cannot stop smoking should be advised to switch to lower-yield cigarettes. We studied "tar" (estimated by urine mutagenicity), nicotine, and carbon monoxide exposure in habitual smokers switched from their usual brand to high- (15 mg of tar), low- (5 mg of tar), or ultralow-yield (1 mg of tar) cigarettes. There were no differences in exposure comparing high- or low-yield cigarettes, but tar and nicotine exposures were reduced by 49% and 56%, respectively, and carbon monoxide exposure by 36% while smoking ultralow-yield cigarettes. Similarly, in 248 subjects smoking their self-selected brand, nicotine intake, estimated by blood concentrations of its metabolite cotinine, was 40% lower in those who smoked ultralow but no different in those smoking higher yields of cigarettes. Our data indicate that ultralow-yield cigarettes do deliver substantial doses of tar, nicotine, and carbon monoxide, but that exposures are considerably less than for other cigarettes.

Psoriasis. How to keep mild disease from becoming severe.

Progress in care of mild psoriasis has been slight. Good, practical therapy of mild disease emphasizes organization of and strict compliance to well-known therapies rather than use of new therapies. Of greatest importance is prevention of disabling severe disease. For severe psoriasis, which occurs infrequently, care is best assigned to dermatologists with special experience. Advances in oncology, bacteriology, and photobiology have led to new and effective treatments for severe disease. Because psoriasis is so poorly understood, physicians should be restrained from making claims about its causes and aggravating influences. Every affected patient deserves to be thoroughly informed about the disease and helped to obtain independence through an inexpensive therapeutic regimen that can be adapted to his or her job, income level, and lifestyle. There is no simple cure for psoriasis today.

[Anti-inflammatory activity of the dry distillation tar of delipidated soybean (Glyteer) (1)].

The anti-inflammatory activity of the dry distillation tar of delipidated soybean (GL, 0.1 approximately 10%) was investigated by its topical application to mice, rats and guinea pigs; and the effects were compared with those of betamethasone 17-valerate (BV, 0.12%), ibuprofen (IP, 5%), phenylbutazone (PB, 5%) and flufenamic acid (FA, 5%), which were all prepared with the same ointment base. GL (1 approximately 10%) showed a concentration-dependent inhibition of the increased vascular permeability induced by histamine and bradykinin in guinea pigs. GL significantly inhibited rat paw edema induced by carrageenin, but in serotonin-induced paw edema, GL showed only a weak effect. GL also inhibited the erythema formation induced by ultra-violet rays, and the activity was equal to that of PB. The inhibitory potency of GL against the erythema formation induced by arachidonic acid in guinea pigs was equal to that of IP. It is suggested from these results that the mode of action of GL is similar to that of other acidic non-steroidal anti-inflammatory drugs. However, GL did not inhibit paper disk granuloma in rats. Furthermore, GL markedly inhibited the delayed-type hypersensitivity induced by picryl chloride, and the activity was stronger than that of IB, PB and FA. Here GL showed the mode of action seen with steroidal anti-inflammatory drugs. The present data provide evidence that GL applied externally possesses a potent effect as an anti-inflammatory drug.

Improvement of the efficacy and safety of oral methoxsalen photochemotherapy.

To improve efficacy and safety of psoralen plus UV radiation at 320-400 nm (PUVA), investigators designed different therapeutic approaches. Our goals are to minimize the acute risks and lower the long-term hazards. Some of these therapeutic approaches focus on dosimetry and intensity of PUVA and some on combining PUVA with other therapeutic modalities. Both approaches try to minimize the total number of treatments and to decrease the amount of UVA radiation delivered to the patient and, as a result, decrease the total skin insult.

[The effect of a tar admixture to dithranol-salicylic-acid-white-petrolatum therapy on the cytokinetics of psoriasis]. / Einfluss von Teerzusatz zur Cignolin-Salicylsäure-weisse-Vaselin-Therapie (CSV) auf die Zytokinetik der Psoriasis (TCSV-Therapie).

The initial stimulation of DNA-synthesis after application of dithranol as single agent is completely inhibited by addition of tar. The autoradiographic analyse indicates that the good clinical effect of the new antipsoriatic therapy with TCSV may be due to suppression of dithranol-caused irritation by tar. But, restored cytokinetic values do not correspond to clinical remission of psoriasis.

Modified Goeckerman therapy for psoriasis. A two-year follow-up of a combined hospital-ambulatory care program.

Two groups totaling 162 patients hospitalized for modified Goeckerman treatment of severe psoriasis were matched for sex, age, and season of admission and followed up for two years after discharge. One group remained hospitalized throughout their average 20.8-day course; the other half was hospitalized 14 days, then transferred to an ambulatory center for the remainder of a course averaging 20.8 days. No difference was detected between the groups in the duration that improvement equaled or exceeded progress achieved at discharge. The percentage of patients remaining continuously improved after discharge was 80% at one month, 55% at six months, 40% at 12 months, and 20% at 24 months. rates of relapse requiring readmission or alternate therapy were also similar: 75% had not relapsed by 12 months and 60% had not relapsed by 24 months.